Clinical Trials Register

Summary
EudraCT Number:	2010-019844-38
Sponsor's Protocol Code Number:	A6141116
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-30
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2010-019844-38

A.3

Full title of the trial

A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL EVALUATING THE SAFETY AND EFFICACY OF EARLY TREATMENT WITH EPLERENONE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Clinical trial exploring treatment benefits and safety of early administration of eplerenone in patients with heart attacks compared with placebo.

A.3.2

Name or abbreviated title of the trial where available

Reminder Study

A.4.1

Sponsor's protocol code number

A6141116

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01176968

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pfizer Inc., 235 East 42nd Street, New York, NY 10017
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pfizer Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pfizer Inc
B.5.2	Functional name of contact point	Clinical Trials.gov Call Center
B.5.3	Address:
B.5.3.1	Street Address	235 East 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017
B.5.3.4	Country	United States
B.5.4	Telephone number	0018007181021
B.5.5	Fax number	001303739 1119
B.5.6	E-mail	ClinicalTrials.govCallCentrere@pfizer.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Inspra®
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer bv
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	eplerenone
D.3.9.1	CAS number	107724-20-9
D.3.9.2	Current sponsor code	SC-66110
D.3.9.3	Other descriptive name	Pregn-4-ene-7,21-dicarboxylic Acid,9,11-epoxy-17-hydroxy-3-oxo, γ-lactone, methyl ester,(7α,11α,17α)
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

ACUTE MYOCARDIAL INFARCTION

E.1.1.1

Medical condition in easily understood language

Heart Attack

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10000891
E.1.2	Term	Acute myocardial infarction
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is:
To assess the impact of eplerenone on cardiovascular mortality and morbidity in patients with acute myocardial infarction (STEMI) when initiated within the first 24 hours of onset of symptoms (preferably during the first 12 hours).

E.2.2

Secondary objectives of the trial

The secondary objective is:
To investigate the effect of eplerenone on serum biomarkers of collagen metabolism / myocardial fibrosis (eg, ICTP, PINP, PIIINP) and cardiovascular risk (eg, ADMA, adiponectin) and to potentially relate these measures to clinical outcomes.
Safety will be assessed throughout the study by a Data and Safety Monitoring Board (DSMB), reviewing the incidence of nature of adverse events reported in each group.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into this study.
1. Evidence of a personally signed and dated Informed Consent Document obtained prior to the initiation of any study procedures and indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Subjects must be male or non-pregnant female aged ≥ 18 years of age at the time informed consent is obtained.
4. If the subject is female, she must be post-menopausal, or is surgically sterile, and is not lactating.
5. Subjects must have experienced a myocardial infarction (STEMI) within the previous 24 hours confirmed by symptoms and ECG.
STEMI is defined by:
1. Chest pain/discomfort lasting for 20 minutes or more of ischaemic characteristics (epigastric or interscapular are included).
2. ST segment elevation at the J point in two or more contiguous leads with the cut off points ≥ 0.2 mv in leads V1, V2 or V3 and ≥ 0.1 mv in other leads (contiguity in the frontal plane is defined by the lead sequence aVL, I, inverted aVR, II, aVF, III).
or New left bundle branch block.
3. Blood levels of cardiac enzymes are not required for a diagnosis of STEMI; however, if levels are available at time of randomization, then Troponin (I or T) OR creatine kinase (CK-MB, gender specific values should be used) must exceed the 99th percentile of normal of the laboratory performing the assay. Subjects randomized without subsequently elevated cardiac enzymes will continue in the study. A separate subgroup analysis will be performed.

E.4

Principal exclusion criteria

Subjects presenting with any of the following will not be included in the study:
1. The subject has received any investigational medication or used any investigational device within 30 days prior to the first dose of study medication or is actively participating in any investigational drug or device study, or is scheduled to receive an investigational drug other than eplerenone or to use an investigational device during the course of the study.
2. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. Subjects who have experienced a previous myocardial infarction may be included provided all other inclusion / exclusion criteria are met.
3. Subjects with inability to follow protocol procedures according to the investigation.
4. The subject has any condition which, in the opinion of the Investigator, makes participation in this study not in the best interest of the subject.
5. The subject has a severe organic disorder or has had surgery or disease of the gastrointestinal tract which, in the opinion of the Investigator, may interfere with the absorption, pharmacokinetics, or elimination of the study drug.
6. The subject has a co-morbid condition that would be expected to result in death during the next year (eg, terminal cancer, AIDS, etc) including subjects receiving immunosuppressive or antineoplastic therapy.
7. The subject has current evidence of alcohol or drug abuse problems, which in the Investigator's opinion, precludes study participation.
8. Subjects treated with eplerenone or other aldosterone antagonists within the past 1 month.
9. The subject has an implanted cardiac defibrillator (ICD).
10. The subject is awaiting cardiac transplant.
11. The subject has uncontrolled hypotension (SBP<90mmHg).
12. Subjects with eGFR ≤30ml/min (based on admission serum creatinine and the MDRD formula) or serum creatinine ≥220µmol/L.
13. Subjects with a known low ejection fraction of less than 40% or any previous history of heart failure.
14. Patients who have haemodynamically relevant aortic or mitral valve stenosis as judged by the investigator.
15. Subjects with a diagnosis of hypertrophic cardiomyopathy.
16. Subjects who have had cardiac surgery within 30 days prior to randomization.
17. Concomitant use of potassium sparing diuretics (eg, spironolactone, triamterene or amiloride) or subjects who in the opinion of the investigator require treatment with potassium sparing diuretics.
Use of potassium preparations or supplements will be allowed on a case by case basis at the discretion of the Investigator.
18. Concomitant use of potent cytochrome p450 3A4 (CYP3A4) inhibitors, such as but not limited to: ketoconazole; itraconazole; nefazodone; troleandomycin; clarithromycin; ritonavir; nelfinavir (see Appendix 3 of the protocol).
19. Concomitant use of cytochrome p450 3A4 (CYP3A4) inducers, such as but not limited to: St. John’s wort; rifampin; carbamazepine; phenytoin; phenobarbitol (see Appendix 3 of the protocol).
20. Subjects who are likely to require treatment during the trial period with drugs not permitted by this protocol.
21. Subjects with preexisting significant hepatic disease (for example, known positive serology for viral hepatitis) or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 times the upper limits of normal.
22. Subjects with a known sensitivity or intolerance to eplerenone, spironolactone or tablet excipients.
23. Donation of blood or blood products for transfusion at any time during the trial or until 30 days after completion of treatment.
24. Prisoners or subjects who are compulsorily detained (involuntary incarcerated) for treatment of either a psychiatric or physical illness must not be enrolled into this study.
25. The subject has been previously admitted to the study.

E.5 End points

E.5.1

Primary end point(s)

Composite primary endpoint:
Time to first event of cardiovascular mortality, re-hospitalization or extended initial hospital stay due to diagnosis of heart failure, sustained ventricular tachycardia or fibrillation, ejection fraction ≤ 40% after 1 month or BNP >200 pg/ml or NT-proBNP >450 pg/ml (age<50 years); >900 pg/ml (age 50-75 years) or >1800 pg/ml (age>75 years) after 1 month.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 week, 4 weeks, 3, 6 and 12 months

E.5.2

Secondary end point(s)

1. Time to cardiovascular mortality.
2. Time to diagnosis of heart failure.
3. Time to first and each subsequent episode (after an event free interval of ≥ 48 hours) of
sustained ventricular tachycardia or ventricular fibrillation.
4. Time to first recorded ejection fraction of ≤ 40% (recorded 1 month or later postrandomization).
5. Time to BNP >200 pg/ml or NT-proBNP >450, >900 or >1800 pg/ml for ages <50 years,
50-75 years and >75 years, respectively (recorded 1 month or later post-randomization).
6. Time to decision to provide an implantable cardioverter defibrillator (ICD) or cardiac
resynchronization therapy (CRT).
7. Time to second or subsequent non-fatal myocardial infarction.
8. QRS duration at 6 months post-randomization.
9. Left atrial diameter (recorded on each occasion an echocardiogram is conducted).
10. Change in serum levels of biomarkers at 6 months post-randomization. Blood samples
for biomarkers will be stored and analyzed post completion of the study.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 week, 4 weeks, 3, 6 and 12 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Subjects will receive standard therapy (refer to protocol section 3)

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Czech Republic

France

Germany

Greece

Hungary

Netherlands

Poland

Slovakia

Spain

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

As per Protocol

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

708

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

304

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Under circumstances when the subject is unable to provide informed consent (eg, dosed with morphine or in significant distress), informed consent should be sought from a legally acceptable representative such as next of kin.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

962

F.4.2.2

In the whole clinical trial

1012

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

No study drug will be provided after the patient’s participation in the study is completed.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-09-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-07-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-10-29

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